Insulin Refresher slides Date of preparation: June 2017 Review date: June 2018 Prepared by Donna Chorley, Pharmacist

Insulin refresher session Types of insulin Insulin regimens Insulin errors Intravenous insulin Variable Rate Intravenous Insulin Infusion (VRIII) Perioperative insulin use

INSULIN TYPES

Types of insulin Rapid acting analogue Short acting (human) Intermediate acting (human) Long acting analogue Biphasic mixtures (human; analogue) Porcine and bovine rarely used

INSULIN PROFILES

Rapid acting analogues NovoRapid (aspart) Humalog (lispro) Apidra (glulisine) ↓ risk of hypoglycaemia Short acting insulin Soluble insulin Actrapid; Humulin S; Insuman Rapid Slower onset Longer duration

Intermediate – Isophane Long-acting analogues Insulatard; Humulin I; Insuman Basal Provides background (basal) insulin (Type 2 patients) Long-acting analogues Levemir (detemir) Lantus (glargine) Tresiba (degludec) (42 hrs) Basal insulin (Type 1 & some Type 2)

Biphasic Human Humulin M3 Insuman Comb 15 Insuman Comb 25 Insuman Comb 50 Biphasic analogues NovoMix 30 Humalog Mix25 Humalog Mix50

Insulin regimens

Insulin Regimens There is no single regimen that will suit all people Lifestyle and eating habits need to be taken into consideration when deciding which regimen to use Aim is to provide sufficient background (BASAL) insulin with BOLUS insulin to cover meals

Normal insulin secretion Short-lived, rapidly generated meal-related insulin peaks 70 60 50 40 Insulin (µU/ml) Low, steady, basal insulin profile 30 20 In healthy adults, normal insulin secretion has two key elements: short-lived, rapidly generated peaks in response to food intake, complemented by a low level of basal insulin to control glucose between meals. References Polonsky KS, Given BD, Van Cauter E. Twenty-four-hour profiles and pulsatile patterns of insulin secretion in normal and obese subjects. J Clin Invest 1988;81:442–8 10 6:00 10:00 14:00 18:00 22:00 2:00 6:00 Time of day Polonsky KS et al. J Clin Invest 1988;81:442–8

Insulin regimens As a guideline – the more active the lifestyle the more fast acting insulin would be used. If the patient is still producing their own insulin but in insufficient quantities ie type 2 a single injection may be sufficient – usually in combination with an OHA. The most common regimen is bd mix, the most common being 30% soluble insulin. It is not certain that more frequent injections give better control but it does give a greater flexibility of lifestyle

Basal Bolus regimen Allows greater flexibility Uses rapid acting insulin just before each meal Long acting insulin (Analogues can be given at any time but must be given same time every day) Patients can adjust their dose according to CBG level, exercise and quantity of CHO to be eaten

Twice Daily regimen Most common regimen used in UK Biphasic insulin Suitable for those with regular meal times and diet Shorter acting component Controls rise in glycaemic level after breakfast and evening meal Longer acting component Maintains glycaemic control from lunch until the early part of the evening and from late evening until the next morning Snacks may be needed between meals and before bed to prevent hypoglycaemia

Once Daily Insulin Type 2 only Use of intermediate or long acting insulin Insulatard, Humulin I Lantus or Levemir (NICE criteria) Needs to be given same time daily Can be used in combination with oral antidiabetic medicines (SFU, gliptins) Adjusted depending on pre breakfast blood glucose level

INSULIN ERRORS

Potential errors Omission Insulin name / insulin type Administration time Insulin dose Transfer of information Transcription Discharge (to GP, to community nurse) Use of “u” or “iu” instead of units Wrong syringe

Avoiding omission Know who is on insulin Always prescribe on main prescription chart as: “Insulin – see diabetic chart” Endorse supplementary chart section Plan ahead: Ensure breakfast dose for next day prescribed If patient stable prescribe weekend doses in advance Ensure sufficient insulin in pen/vial for next 2 doses If insulin due after a hypo Treat hypo Give insulin after dose review (with meal)

Insulin Names Use brand names Always write name in full Humalog Mix 25 Humulin I NovoMix 30 Common errors Humalog instead of Humalog Mix 25 Humulin instead of Humulin I or Humulin M3 NovoRapid instead of NovoMix 30 Lantus / Levemir confused

Doses Variable Type 1 patients generally lower doses Type 2 patients generally higher doses Idea from King’s College Hospital Rapid / short acting or biphasic insulin Confirm all doses over 25 units Intermediate / long-acting insulins Confirm all doses over 50 units If patients carbohydrate counting Prescribe meal insulin as dose range e.g. 2 to 6 units Record number of units taken

Units Never abbreviate units The use of “u” and “i.u” can be misread - 10 fold increase in dose given SGUH chart pre-printed “units” Remember to write units in full for stat doses and for dose records Leave a space between dose and units 22 units not 22units

Administration times Rapid acting / (short acting) Always for meals Intermediate – isophane Once or twice daily Usually bedtime if once daily May be given in morning Long-acting analogues Anytime but must be same time everyday Biphasic mixtures

Insulin Syringe Insulin syringes must be used to measure and administer insulin doses unless a pen device is used Non-insulin syringes never used If staff administering insulin must use safety insulin syringes

Insulin Pens and Cartridges One pen – one patient Store in patient’s POD locker Stable at room temperature for 4 weeks Discard all insulin 4 weeks after opening Do not withdraw insulin from a pen or cartridge with a syringe If staff administering insulin must use safety needles (Patients who self-administer should use standard insulin pen needles)

Insulin Strength All formulary insulins at SGUH 100 units in 1ml Be aware of higher strength insulins Tresiba 200 units in 1ml (Flextouch pen) Humalog 200 units in 1ml (Kwikpen) Toujeo 300 units in 1ml (Solostar pen)

Biosimilar insulins Not currently stocked at SGUH Abasaglar (insulin glargine 100 units in 1ml) Toujeo (insulin glargine 300 units in 1ml) Be aware not directly interchangeable with Lantus insulin Seek advice if patient admitted without own supply Dose reduction needed for switch to Lantus

Planning for discharge Is patient new on insulin? Can they self administer? Refer to Diabetes Specialist Nurse before discharge – at least 48 hours notice Is a nurse needed to administer / monitor? Notify community team ≥ 48 hours before discharge Ensure insulin name, dose and times due are clear TTO documentation Insulin name and device Dose at discharge and whether changed Use duration box if necessary Request sufficient pens for 2 weeks if supply needed

INSULIN MONITORING

Glucose monitoring Capillary blood glucose (CBG) Lab sample if CBG “Hi” How frequently? Any specific situation? Target range for inpatients: 5 – 7 mmol/L (pre-meal) Higher levels preferred for frail, older patients

Ketone monitoring Important for patients with type 1 diabetes Monitor for ketones During periods of acute illness eg infection, stress, GI disturbances When CBG > 14 mmol/litre During pregnancy Presence of ketones indicates: Need for therapy change Possible impending / established ketoacidosis

Adjusting insulin doses Basal bolus: Adjust basal insulin to correct fasting glucose Adjust bolus insulin dose for previous meal e.g. adjust breakfast insulin if pre-lunch BG high/low Twice daily biphasic: The breakfast injection affects the lunchtime and evening meal blood glucose The evening injection affects the bed time level and the fasting level the next day

Insulin Titration Adjust after several readings – review the trends Every action has a consequence – make one adjustment at a time Eliminate all hypoglycaemic episodes first If need to reduce insulin dose – 10 to 20% reduction Start the day with good glucose levels – if CBG high throughout day normalise fasting level first If need to increase insulin dose - 10% increment DON’T prescribe prn insulin Facilitator Notes What are the current blood glucose targets? Why is it important ot achieve good glycaemic control? Does the required glucose monitoring frequency differ with the insulin regime? Is it safe to prescribe as required /PRN short-acting insulin to treat hyperglycaemia?

Insulin titration cont’d PRIOR to adjusting DON’T forget to check: Injections Sites – where is the insulin being injected? What is the patient eating or drinking? Has any new medication been initiated that could have affected the glucose levels? Has the right insulin been prescribed?

Prescription review Review the type of insulins patient is taking Why is patient on basal insulin and a biphasic? Why is the patient taking biphasic insulin and gliclazide? Are the administration times correct? Rapid/short and biphasic never given at bedtime

Intravenous insulin

Intravenous insulin – Indications NBM (variable rate) Peri-operative / Peri-procedure (variable rate) DKA / HHS (fixed rate) Patients who are vomiting (variable rate) Patients with hyperglycaemia complicating acute renal, cardiac or liver failure (variable rate) Treatment of hyperkalaemia (fixed rate)

Variable Rate Intravenous Insulin Infusion VRIII

Risks / Benefits Advantages of VRIII Disadvantages of VRIII Flexibility for independent adjustment of fluid and insulin Accurate delivery of insulin via syringe driver Allows tight BG control in the intra-operative starvation period Disadvantages of VRIII Risk of adverse events leading to serious incidents Reactive to BG levels not proactive Increased staff time for monitoring Delays and difficulties in transfer back to normal regimen may prolong length of stay

Insulin infusion rate Rate determined by: Insulin sensitivity Type 1 patient on low dose subcutaneous insulin dose is sensitive to insulin and requires lower rate Type 2 patient on large subcutaneous insulin doses is insulin resistant and requires higher rate Whether long-acting insulin given in previous 12 hours If Lantus or Levemir given basal requirements met and can infuse at lower rate with a zero option If no basal insulin given need continuous infusion

Oral anti-diabetic agents but no s/c insulin – initial scale 1 or 2

Fluid management with iv insulin Provide glucose as substrate (fuel) to prevent proteolysis, lipolysis and ketogenesis Optimise intravascular volume status Maintain serum electrolytes within normal ranges Current recommendations 0.45% NaCl + 5% glucose + 0.15% KCl 0.45% NaCl + 5% glucose + 0.3% KCl

Monitoring Capillary Blood Glucose (CBG) Every hour If out of range increase frequency Potassium Ideally every 4 hours (VRIII) In practice if in range 2 readings in 24 hours acceptable Sodium Cannula and infusion devices Duration Refer to diabetes team if duration > 24 hours

Monitoring blood glucose Monitor CBG every hour Aim for CBG range 6 to 10 mmol/L If hyperglycaemia CBG >12 mmol/L for 3 readings and not falling by ≥ 3mmol/L per hour Ensure infusion devices and cannula patent Prescriber to increase to next scale If hypoglycaemia (CBG < 4mmol/L) Reduce rate to 0.5 units/hour If scale zero stop infusion until hypoglycaemia treated Treat hypoglycaemia Adjust scale once CBG > 4mmol/L

Successful IV Insulin Infusion Mmol/l 10 6 Desired Pattern Desired Pattern Undesirable Pattern

Hypoglycaemia Most common side effect of iv insulin Prevent by frequent CBG monitoring Treat for “hypo avoidance” Adjust insulin dose 100 ml 10% glucose iv prn prescription

Stopping iv insulin Patient eating and drinking; not vomiting Intravenous insulin Half life 3 to 5 minutes Duration 20 to 30 minutes First dose of subcutaneous insulin must be given 60 minutes before stopping iv If basal insulin (Levemir, Lantus, Tresiba) continued alongside VRIII can stop VRIII at any time

Perioperative management

Perioperative management VRIII not required if following criteria met: HbA1c < 69 mmol/mol CBG between 5 and 11 mmol/L Short starvation period (missing one meal) Consider VRIII if any of following apply: Poorly controlled diabetes and cannot postpone surgery Missing > one meal Type 1 diabetes and no background insulin

Prescribing guidance on the initiation of VRIII for elective surgeries Missing only one meal⌘ Missing Two meals Type I Type II No Missing basal insulin♯ CBG between 5-11 mmol/ml on admission Surgery in the morning initiate VRIII by 8 AM Surgery in the afternoon initiate VRIII by 12 noon Yes No Yes Initiation of VRIII is not necessary monitor Blood Glucose hourly before and during Procedure/Surgery and 2 hourly post Surgery ♯ Any long/intermediate acting or biphasic insulin ⌘ When the period of NBM is extended from missing only one meal to missing two meals, then VRIII should be initiated as soon as possible Recent HbA1c < 69 mmol/mol Yes

Morning Surgery Day before surgery - all insulin as usual Day of surgery Long- acting analogue Continue am dose (if recent hypos ↓ dose by 1/3) Intermediate acting Half morning dose If to have VRIII omit morning dose Rapid acting Omit morning dose Biphasic (mixed) If T1DM or missing > 1 meal – will need VRIII

Afternoon Surgery Day before surgery - all insulin as usual Day of surgery Long- acting analogue Continue am dose (if recent hypos ↓ dose by 1/3) Intermediate acting Half morning dose If to have VRIII give usual morning dose Rapid acting Give usual morning dose with breakfast Omit lunchtime dose Biphasic (mixed) Give half morning dose with breakfast

VRIII – Start time Morning surgery If well controlled diabetes initiate VRIII by 08:00 hours If poorly controlled initiate VRIII earlier Consider starting overnight Afternoon surgery If well controlled diabetes initiate VRIII by 12:00 noon

Free e-learning module available: the six steps to insulin safety For all healthcare professionals who manage patients on insulin Overall aim of reducing insulin errors in clinical practice Developed by the Primary Care Diabetes Society, in association with the nursing group TREND-UK Log in or register for free on the Diabetes on the net website  http://www.diabetesonthenet.com/ 

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